Functionalized 2,2′-bipyridines and 2,2′:6′,2″-terpyridines via stille-type cross-coupling procedures

Article abstract of DOI:10.1021/jo0260600

Stille-type cross-coupling procedures are utilized in order to prepare a variety of functionalized 2,2′-bipyridines and 2,2′:6′,2″-terpyridines. Such N-heterocyclic compounds are of great interest as chelating ligands for transitionmetal ions in the field of supramolecular chemistry. Various mono- and disubstitued 2,2′-bipyridines were synthesized in high yields and multigram scales using a modular design principle. The terpyridines may be functionalized in one step with different substituents at the outer pyridine rings and at the 4′-position of the centered ring, leading to multifunctionalized compounds. The initially obtained methyl ester and ethyl ester groups can be simply converted into bromomethyl and hydroxymethyl groups which allow further functionalization reactions.

Full text of DOI:10.1021/jo0260600

useful multifunctional chelating agents, which may form
metal complexes with special photo- and electrochemical
properties14-17 or can be utilized as supramolecular
initiators for different types of controlled polymerization
procedures.18-20
F u n ction a lized 2,2′-Bip yr id in es a n d
2,2′:6′,2′′-Ter p yr id in es via Stille-Typ e
Cr oss-Cou p lin g P r oced u r es
Marcel Heller and Ulrich S. Schubert*
Macromolecular Chemistry and Nanoscience and Center for
Nanomaterials (cNM), Eindhoven University of Technology,
PO Box 513, 5600 MB Eindhoven, The Netherlands
Stille-type cross-coupling procedures enable the well-
directed introduction of methyl substituents into any 2,2′-
bipyridine ring position.21 In particular, the unsymmet-
rically disubstituted methylbipyridines are not as common.
The 4,6′- and the 4,5′-dimethyl-2,2′-bipyridines have been
reported previously only as byproducts of the reaction of
pyridine N-oxides with pyridine derivatives.22,23 Starting
from the cheap aminopicolines 1a -c, the corresponding
bromopicolines 2a -c can be obtained in hundred gram
quantities by a simple diazotation/bromination sequence
(Scheme 1).24,25 The bromopicolines can be utilized on one
hand as one coupling agent for the Stille coupling and
on the other hand for the further conversion to the
2-tributylstannylpyridines 3a -c, which then act as the
second coupling partner. The stannylation of the bromo
compounds via n-butyllithium and the following trans-
metalation step can be performed nearly quantitative in
the case of the 5- and 6-methyl-2-tributylstannylpyridine
3a and 3b.
u.s.schubert@tue.nl
Received J une 14, 2002
Abstr a ct: Stille-type cross-coupling procedures are utilized
in order to prepare a variety of functionalized 2,2′-bipy-
ridines and 2,2′:6′,2′′-terpyridines. Such N-heterocyclic com-
pounds are of great interest as chelating ligands for transition-
metal ions in the field of supramolecular chemistry. Various
mono- and disubstitued 2,2′-bipyridines were synthesized in
high yields and multigram scales using a modular design
principle. The terpyridines may be functionalized in one step
with different substituents at the outer pyridine rings and
at the 4′-position of the centered ring, leading to multifunc-
tionalized compounds. The initially obtained methyl ester
and ethyl ester groups can be simply converted into bro-
momethyl and hydroxymethyl groups which allow further
functionalization reactions.
The following Stille-type cross-coupling reaction is
carried out in degassed toluene in the presence of
tetrakis(triphenylphosphine)palladium(0) as catalyst. De-
pending on the position of the methyl groups in the
starting materials, the corresponding monomethyl-
substituted bipyridines 4-6 and symmetrically or un-
symmetrically dimethyl-substituted bipyridines 7-12 are
obtained in good yields (Scheme 1). For the synthesis of
the monomethyl functionalized bipyridines 4-6, the
corresponding bromopicolines 2a -c were coupled with
2-tributylstannylpyridine 3d . However, it is also possible
N-Heterocyclic compounds are of major importance in
biological systems. In porphyrine derivatives, they act as
ligands for transition metals and are responsible for
energy conversion and substance transport in cells. In
supramolecular chemistry, oligopyridines are utilized as
bi-, tri-, and multidentate ligands besides the well-known
coronands, cryptands, and podands1,2 and may form
helical or grid-like superstructures.3 Moreover, oligopy-
ridines allow the formation of supramolecular, metal
containing polymers.4 An efficient synthesis of oligopy-
ridines and the introduction of substituents in any ring
position is required for the construction of versatile
metallo-supramolecular architectures. Besides the coup-
ling of organosulfur compounds5 or of lithium pyridines
with CuCl2,6 the most efficient way to well-directed
functionalization of bi- and terpyridines is represented
by modern palladium(0)-catalyzed cross-coupling proce-
dures. Suzuki-,7-9 Negishi-,10,11 and Stille-type coupling
reactions12,13 are distinguished by excellent yields and the
free choice of the substitution positions. Stille-type cross-
coupling provides the possibility to introduce different
functional groups into 2,2′-bipyridines and 2,2′:6′,2′′-
terpyridines in one step. A range of further functional
group conversions described herein opens avenues to
(7) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis 1984, 936.
(8) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(9) Lehmann, U.; Henze, O.; Schlu¨ter, D. Chemistry Eur. J . 1999,
5, 854.
(10) Negishi, E. Current Trends in Organic Synthesis; Pergamon:
New York, 1983.
(11) Savage, S. A.; Smith, A. P.; Fraser, C. L. J . Org. Chem. 1998,
63, 10048.
(12) Stille, J . K. Angew. Chem. 1986, 98, 504; Angew. Chem., Int.
Ed. 1986, 25, 508.
(13) Labadie, J . W.; Stille, J . K. J . Am. Chem. Soc. 1983, 105, 6129.
(14) Armspach, D.; Constable, E. C.; Housecroft, C. E.; Neuburger,
M.; Zehnder, M. J . Organomet. Chem. 1998, 550, 193.
(15) Collin, J . P.; Guillerez, S.; Sauvage, J . P. J . Chem. Soc., Chem.
Commun. 1989, 776.
(16) Hanabusa, K.; Nakamura, A.; Koyama, T.; Shirai, H. Polym.
Int. 1994, 35, 231.
(17) Whittle, B.; Batten, S. R.; J effery, J . C.; Rees, L. H.; Ward, M.
D. J . Chem. Soc., Dalton Trans. 1996, 22, 4249.
(18) Schubert, U. S.; Heller, M. Chem. Eur. J . 2001, 7, 5252.
(19) Schubert, U. S.; Hochwimmer, G.; Heller, M. ACS Symp. Ser.
2002, 812, 163.
(20) Heller, M.; Schubert, U. S. Macromol. Rapid Commun. 2001,
22, 1358.
* To whom correspondence should be addressed. Fax: +31 (0)
402474186.
(1) Constable, E. C. Metals and Ligand reactivity; VCH: Weinheim,
1996.
(2) Constable, E. C., Karlin K. D., Eds. Progress in Inorganic
Chemistry; J ohn Wiley & Sons: New York, 1994; p 67.
(3) Lehn, J . M. Supramolecular Chemistry, Concepts and Perspec-
tives; VCH: Weinheim, 1995.
(4) Schubert, U. S.; Eschbaumer, C. Angew. Chem. 2002, 114, 3016;
Angew. Chem., Int. Ed. 2002, 41, 2892.
(5) Uenishi, J .; Tanaka, T.; Wakabayashi, S.; Oae, S. Tetrahedron
Lett. 1990, 4625.
(6) Parks, J . E.; Wagner, B. E.; Holm, R. H. J . Organomet. Chem.
1973, 56, 53.
(21) Schubert, U. S.; Eschbaumer, C.; Heller, M. Org. Lett. 2000, 2,
3373.
(22) Haginawa, J .; Higichi, Y.; Hirawata, Y.; Hoshino, N.; Sakakura,
H. Yakugaku Zasshi 1979, 99, 1176.
(23) Haginawa, J .; Higichi, Y.; Kawashima, T.; Goto, T. Yakugaku
Zasshi 1975, 95, 204.
(24) Windscheif, P. M.; Vo¨gtle, F. Synthesis 1994, 87.
(25) Eisenbach, C. D.; Go¨ldel, A.; Terskan-Reinold, M.; Schubert,
U. S. Macromol. Chem. Phys. 1995, 196, 1077.
10.1021/jo0260600 CCC: $22.00 © 2002 American Chemical Society
Published on Web 10/19/2002
J . Org. Chem. 2002, 67, 8269-8272
8269

SCHEME 1. P r ep a r a tion of Va r iou s 2,2′-Bip yr id in es w ith Meth yl Su bstitu en ts
SCHEME 2. Dim eth yl-2,2′:6′,2′′-ter p yr id in es via
out 4′-functions, bearing methyl substituents at different
positions of the outer pyridine rings may be obtained via
two “orthogonal” routes of preparation (Scheme 2).
In route A, 2,6-dibromopyridine 14 acts as the central
unit and is coupled with 6-, 5-, or 4-methyl-2-tributyl-
stannylpyridine (3a -c), respectively. The corresponding
methyl-terpyridines 16 and 17 are obtained in good
yields.28-30 The attempt to synthesize 6,6′′-dimethyl-2,2′:
6′,2′′-terpyridine leads to a mixture of different com-
pounds, from whom the desired product may not be
purely separated by common methods. As the main
product, 6-bromo-6′-methyl-2,2′-bipyridine, was detected
by GC-MS investigations. After the first coupling step,
the reaction seems to stop due to the steric and/or
electronic influence of the pyridine ring at the 6-position
of this intermediate. Thereby, the reactivity of the bromo
function is reduced.31 The application of route B finally
enables the synthesis of 6,6′′-dimethyl-2,2′:6′,2′′-terpyri-
dine 15. 2,6-Bis(trimethylstannyl)pyridine 1832 functions
as central coupling agent and may be converted with the
2-bromopicolines 2a -c to yield the terpyridines 15-17.
Therefore, compared to route 1, route 2 represents an
inverse synthetic strategy.
The formation of the versatile multifunctional 2,2′:
6′,2′′-terpyridines can be achieved as mentioned above
by the use of 2,6-dihalogenopyridines additionally func-
tionalized in the 4-position. For this, 2,6-dichloroisoni-
cotinic methyl or ethyl esters 19 or 20 are useful central
building blocks. The Stille cross-coupling with 5-methyl-
2-tributylstannylpyridine 3b leads in high yields to the
corresponding 5,5′′-dimethyl-2,2′:6′,2′′-terpyridine-4′-
esters 21 and 22. Both the central ester group and the
outer methyl groups are available for different function-
alization reactions which are outlined in Scheme 3.
Therefore, such compounds function as basic agents for
different functional group conversions toward multifunc-
tional terpyridine ligands.
Tw o “Or th ogon a l” Stille-Typ e Cou p lin g Rou tesa
a
Positions (and yields) of the methyl substituents: 15 ) 6,6′′
(A, 0%; B, 43%), 16 ) 5,5′′ (A, 90%; B, 69%), 17 ) 4,4′′ (A, 50%; B,
52%).
to prepare these bipyridines utilizing the 2-tributylstan-
nylpicolines 3a -c and 2-bromopyridine. Substituents at
the 3-position are not considered closer due to the intro-
duction of a twisting of the two pyridine rings, by which
the chelating properties disappear. The monomethyl
substituted bipyridines 4-6 could also be obtained via
the more extensive Negishi coupling in excellent yields.11
The methyl groups of the bipyridines can be easily
converted to the corresponding bromomethyl groups by
use of N-bromosuccinimide (NBS) and azoisobutyronitrile
(AIBN) as shown, e.g., in the case of the monomethylbi-
pyridine 13 (see the Experimental Section). The bromo-
methyl group then acts as the key moiety for further
functionalization reactions. In general, the disadvantage
of the simple NBS bromination are the low yields. For
that reason, Fraser et al. have developed another syn-
thesis, where the bromofunction is introduced via sub-
stitution of a trimethylsilyl group in excellent yields.11,26
To avoid the high synthetic and temporal expenditure of
this method, we enhanced the classical NBS bromination
of monomethyl bipyridines by a fast workup of the crude
product, which otherwise rapidly decomposes.
The Stille-type cross-coupling procedures can be also
used for the preparation of functionalized 2,2′:6′,2′′-
terpyridines (see also ref 27 for a first preliminary
communication). The preparation of 2,2′:6′,2′′-terpy-
ridines requires the utilization of 2,6-bis-functionalized
pyridines that act as central building blocks. After the
Stille-coupling, they become the central pyridine unit of
the terpyridine. By the use of 4-functionalized pyridine
compounds, the introduction of functional groups into the
interesting central 4′-position of terpyridines becomes
straightforward. The coupling partners of the central
compound continue to be the 2-bromo- or 2-tributylstan-
nylpyridines 2a -c or 3a -c. 2,2′:6′,2′′-Terpyridines with-
5,5′′-Dimethyl-4′-(hydroxymethyl)-2,2′:6′,2′′-terpyri-
dine 23 can be obtained in very high yield by the
(26) Schubert, U. S.; Eschbaumer, C.; Hochwimmer, G. Tetrahedron
Lett. 1998, 39, 8643.
(27) Heller, M.; Schubert, U. S. Synlett 2002, 5, 751.
(28) Cardenas, D. J .; Sauvage, J .-P. Synlett 1996, 9, 916.
(29) Schubert, U. S.; Eschbaumer, C.; Hochwimmer, G. Polym.
Mater. Sci. Eng. 1999, 80, 193.
(30) Constable, E. C.; Baum, G.; Bill, E.; Dyson, R.; Eldik, R.; Fenske,
D.; Kaderli, S.; Morris, D.; Neubrand, A.; Neuburger, M.; Smith, D.
R.; Wieghardt, K.; Zehnder, M.; Zuberbu¨hler, A. D. Chem. Eur. J . 1999,
5, 498.
(31) Houghton, M. A.; Bilyk, A.; Harding, M. M.; Turner, P.;
Hambley, T. W. J . Chem. Soc., Dalton Trans. 1997, 2725.
(32) Schubert, U. S.; Eschbaumer, C. Org. Lett. 1999, 1, 1027.
8270 J . Org. Chem., Vol. 67, No. 23, 2002

SCHEME 3. In tr od u ction of a n Ester F u n ction
in to th e 4′-P osition a n d F u n ction a l Gr ou p
Con ver sion s
deprotection of the hydroxy function. Instead, gel filtra-
tion and purification by column chromatography are
applied.
Furthermore, the methyl groups of the 5,5′′-dimethyl-
2,2′:6′,2′′-terpyridine-4′-carboxylic esters 21 and 22 may
be brominated via NBS and AIBN in tetrachloromethane.
Depending on the use of the methyl ester or ethyl ester
derivative, the yields obtained differ considerably. Bro-
mination of the methyl ester produces only 10% of the
corresponding bis(bromomethyl)terpyridine 27, whereas
the 5,5′′-bis(bromomethyl)-2,2′:6′,2′′-terpyridine-4′-ethyl
ester 28 can be isolated in approximately 70% yield. This
result is most probably caused due to the purification
method applied. Up to now recrystallization is the only
way to recover the bis(bromomethyl) compounds because
chromatographic separation could not yet be realized.
Therefore, the influence of the solubility and the tending
to crystallize are the most important factors for the
different yields. However, in the case of the ethyl ester,
it was not yet possible to avoid multiple bromination or
to purify the resulting mixture, as it was also observed
for similar terpyridine derivatives.34
Bromomethyl groups are suitable for almost any nu-
cleophilic substitution reactions. As one example, the
formation of 5,5′′-bis(acetoxymethyl)-2,2′:6′,2′′-terpyridine
4′-ethyl ester 29 is presented, which can be obtained by
the reaction of 28 with pure acetic acid and sodium
acetate in 70% yield. The acetate groups formally act as
protective groups of the corresponding hydroxy functions
and are therefore a potential starting point for a series
of further derivatizations.
SCHEME 4. Alter n a tive Rou te to 4′-TBDMSO-
ter p yr id in e 26 via Dir ect Stille Cou p lin g
In this contribution, Stille-type cross-coupling proce-
dure is shown to be an easy and universal way toward a
large variety of substituted and functionalized bi- and
terpyridines. The reactants can be seen as building blocks
of a “unit construction system” by which the well-aimed
introduction of functional groups into oligopyridines is
possible. The terpyridines can be functionalized in one
step with different substituents at the outer pyridine
rings as well as at the 4′-position of the centered ring.
The obtained terpyridines with methyl ester and ethyl
ester units can be simply converted into the correspond-
ing bromomethyl and hydroxymethyl derivatives, which
are common moieties for further reactions. Therefore,
new functionalized terpyridines are accessible as valuable
chelating ligands with additional potential applications
besides their well-known photo- and electrochemical
properties. Several experiments using such multifunc-
tionalized terpyridines in the fields of supramolecular
initiators and metallo-supramolecular assemblies are
currently in progress.
reduction of 21 with excess of NaBH4 in methanol. The
reaction of 23 with tert-butyldimethylsilyl chloride
(TBDMSCl) in the presence of imidazole under basic
conditions leads to 26. Protection of the hydroxy func-
tion should enable the unaffected functionalization of the
methyl groups.
Compound 26 is also accessible by direct Stille coupling
with 2,6-dichloro-4-(tert-butyldimethylsilanyloxymethyl)-
pyridine 25 (Scheme 4). Building block 25 is obtained
starting from 2,6-dichloroisonicotinic ethyl ester 20 which
at first can be reduced to the corresponding alcohol 24
with LiAlH4 (for similar reaction see ref 33). Then, the
protective group is introduced by the reaction with
TBDMSCl to yield compound 25. Stille-type cross-
coupling of 25 and 5-methyl-2-tributylstannylpyridine
3b leads to 5,5′′-dimethyl-4′-(tert-butyl-dimethylsilanyl-
oxymethyl)-2,2′:6′,2′′-terpyridine 26. The workup of 26
cannot be carried out as usual because HCl causes the
Exp er im en ta l Section
Bromopicolines 2a -c, 2-tributylstannylpyridines 3a -c and
the methyl substituted 2,2′-bipyridines 4-12 were prepared as
previously reported.21 The synthesis of compound 23 we also
described elsewhere.35 The bromomethyl-2,2′-bipyridine 13 has
been already reported,11,36 although the procedure described
herein is a considerably efficient modified NBS bromination and
(33) Fallahpour, R.-A. Synthesis 2000, 12, 1665.
(34) Ulrich, G.; Bedel, S.; Picard, C.; Tisnes, B. Tetrahedron Lett.
2001, 42, 6113.
J . Org. Chem, Vol. 67, No. 23, 2002 8271

is therefore mentioned. 2,6-Bis-trimethylstannylpyridine 18 was
synthesized according to ref 32.
SO4, and the solvent was removed in vacuo. The crude product
could be crystallized from CH2Cl2 or purified by column chro-
matography (silica, starting from CH2Cl2/CH3OH 100:3 ending
up with CH2Cl2/CH3OH 1:2) to yield 2.8 g (75%) of a white
Gen er a l P r oced u r es. Dim eth yl-2,2′:6′,2′′-ter p yr id in es.
Rou te A. The methyl-2-tributylstannylpyridine 3a -c (3.00 g,
7.85 mmol), 2,6-dibromopyridine 14 (0.75 g, 3.17 mmol), and
tetrakis(triphenylphosphine)palladium(0) (0.29 g, 6.0 mol %)
were refluxed for 4 days in absolute toluene (50 mL). After
removal of the solvent, the black residue was treated with
aqueous HCl (3 × 20 mL, 6 M). The suspension was extracted
with CH2Cl2, and the organic phase was washed again with HCl
(20 mL, 6 M). The aqueous solution was added dropwise into
cold aqueous ammonia (300 mL, 10%). The precipitate was
filtered off, dissolved in CH2Cl2, and dried over Na2SO4, and the
solvent was removed again. The residue was crystallized from
ethyl acetate.
Dim et h yl-2,2′:6′,2′′-t er p yr id in es. R ou t e B. 2,6-Bis(tri-
methylstannyl)pyridine 18 (12.23 g, 7.66 mmol), the 2-bromo-
methylpyridine 2a -c (3.29 g, 19.15 mmol), and tetrakis(tri-
phenylphosphine)palladium(0) (0.6 g, 6 mol %) were refluxed in
dry toluene (70 mL) for 72 h at 110 °C. After removal of the
solvent, the black residue was treated with aqueous HCl (3 ×
20 mL, 6 M). The suspension was extracted with CH2Cl2, and
the organic phase was washed again with HCl (20 mL, 6 M).
The aqueous solution was added dropwise into cold aq ammonia
(300 mL, 10%). The precipitate was filtered off, dissolved in
CH2Cl2, and dried over Na2SO4, and the solvent was removed
again. The residue was crystallized from ethyl acetate.
5-Br om om eth yl-2,2′-bip yr id in e (13). 5-Methyl-2,2′-bipyri-
dine 5 (3.0 g, 17.7 mmol), NBS (3.1 g, 18.0 mmol), and AIBN
(40 mg) were refluxed for 2 h in dry CCl4 (80 mL). Then, the
suspension was filtrated. After removal of the solvent in vacuo,
n-hexane (40 mL) was added immediately to the remaining oil.
The mixture was stirred for 1 h, wherein a white solid precipi-
tated. The crude product was filtered off, washed with n-hexane
(40 mL), and dried over P2O5 in vacuo. Recrystallization was
carried out in CHCl3 yielding a white solid (2.2 g, 50%): mp 70
°C (ref11 mp 71-73 °C).
5,5′′-Dim eth yl-2,2′:6′,2′′-ter p yr id in e 4′-Meth yl or -Eth yl
Ester (21/22). 2,6-Dichloroisonicotinic acid methyl or ethyl ester
19/20 (24.3 mmol), 5-methyl-2-tributylstannylpyridine 3b (23 g,
60.7 mmol), and tetrakis(triphenylphosphine)palladium(0) (1.7
g, 6 mol %) were dissolved in dry toluene (100 mL) and refluxed
for 48 h at 110 °C. After removal of the solvent, the black residue
was treated with aq HCl (70 mL, 6 m). The suspension was
filtered and then extracted with CH2Cl2 (2 × 30 mL), and the
organic phase was washed again with HCl (10 mL, 6 M). The
aqueous solution was added dropwise into cold aq ammonia (300
mL, 10%). The precipitate was filtered off, dried in vacuo over
P2O5, and crystallized from ethyl acetate to yield a white solid.
21: 5.0 g, 63%; mp 157 °C; 1H NMR (CDCl3) δ 2.40 (s, 6 H),
3.98 (s, 3 H), 7.63 (m, 2 H′), 8.47 (d, J ) 8.2 Hz, 2 H), 8.53 (m,
2 H), 8.90 (s, 2 H). 22: 5.9 g, 65% (ref37 37%); mp 245 °C (ref37
mp 245-246 °C).
4′-Hydr oxym eth yl-5,5′′-dim eth yl-2,2′:6′,2′′-ter pyr idin e (23).
To a suspension of 5,5′′-dimethyl-2,2′:6′,2′′-terpyridine 4′-methyl
ester 21 (4.00 g, 12.5 mmol) in absolute methanol (200 mL) was
added NaBH4 (0.95 g, 25 mmol) in small portions. The mix-
ture was refluxed for 24 h. Every 6 h, additional NaBH4 (0.47
g, 12.5 mmol) was added. After removal of the solvent, aqueous
Na2CO3 (30 mL, 10%) was added, and the mixture was extracted
with chloroform (3 × 30 mL) under reflux. The combined organic
phases were washed with water and brine and dried over Na2-
1
powder: mp 249 °C; H NMR (CDCl3) δ 2.37 (s, 6 H), 3.63 (s, 1
H), 4.81 (s, 2 H), 7.60 (m, 2 H), 8.32 (s, 2 H), 8.42 (d, J ) 7.98
Hz, 2 H), 8.46 (s, 2 H).
4′-(ter t-Bu tyld im eth ylsila n yloxym eth yl)-5,5′′-d im eth yl-
2,2′:6′,2′′-ter p yr id in e (26). Rou te A. A mixture of 4′-hy-
droxymethyl-5,5′′-dimethyl-2,2′:6′,2′′-terpyridine 23 (1.0 g, 3.4
mmol), TBDMSCl (0.56 g, 3.7 mmol), imidazole (0.51 g, 7.4
mmol), and 4-(dimethylamino)pyridine (0.1 g) in absolute DMF
(30 mL) was stirred for 24 h at 40 °C. After addition of aqueous
NaHSO4 solution (150 mL, 1 M) and diethyl ether (200 mL),
the phases were separated and the aqueous phase was extracted
with diethyl ether (2 × 40 mL). After washing with brine (30
mL), the solvent was removed in vacuo. The crude product was
crystallized from hexane to yield colorless crystals: yield 1.1 g,
80%; mp 137 °C; 1H NMR (CDCl3) δ 0.13 (s, 6 H), 0.96 (s, 9 H),
2.49 (s, 6 H), 4.82 (s, 1 H), 7.66 (dd, J ) 8.01, 1.52 Hz, 2 H), 8.36
(s, 2 H), 8.49 (d, J ) 8.01 Hz, 2 H), 8.52 (s, 2 H).
4′-(ter t-Bu tyld im eth ylsila n yloxym eth yl)-5,5′′-d im eth yl-
2,2′:6′,2′′-ter p yr id in e (26). Rou te B. 2,6-Dichloro-4-(tert-bu-
tyldimethylsiloxy)methylpyridine 25 (1.0 g, 3.42 mmol), 2-tribu-
tylstannyl-5-methylpyridine 3b (3.3 g, 8.6 mmol), and Pd(PPh3)4
(0.5 g) were dissolved in degassed dry toluene and refluxed for
48 h under argon. After cooling, the solvent was removed and
the dark oil was dissolved in CH2Cl2 and filtrated on Al2O3 (A3,
CH2Cl2/MeOH 95:5). The crude product was recrystallized from
hexane to yield colorless crystals: yield 0.8 g, 59%.
5,5′′-Bis(br om om eth yl)-2,2′:6′,2′′-ter p yr id in e 4′-Meth yl or
-Eth yl Ester (27/28). 5,5′′-Dimethyl-2,2′:6′,2′′-terpyridine-4′-
methyl or ethyl ester 21/22 NBS (1.1 eq) and AIBN were refluxed
for 2 h in CCl4. After filtration of the suspension, the solvent
was removed in vacuo. The residue was crystallized twice from
CHCl3. A white solid was obtained. 27: 50 mg, 10%; mp 132 °C;
1H NMR (CDCl3) δ 4.02 (s, 3 H), 4.57 (s, 4 H), 7.92 (m, 2 H),
8.60 (d, J ) 8.2 Hz, 2 H), 8.75 (m, 2 H), 9.00 (s, 2 H). 28: 3.2 g,
1
72%; mp 143 °C; H NMR (CDCl3) δ 1.44 (t, J ) 6.06 Hz, 3 H),
4.47 (q, J ) 7.06 Hz, 2 H), 4.55 (s, 4 H), 7.89 (dd, J ) 8.20, 2.28
Hz, 2 H), 8.56 (d, J ) 8.20 Hz, 2 H), 8.72 (s, 2 H), 9.00 (s, 2 H).
5,5′′-Bis(acetoxym eth yl)-2,2′:6′,2′′-ter pyr idin e 4′-Eth yl Es-
t er (29). 5,5′′-Bis(brommethyl)-2,2′:6′,2′′-terpyridine 4′-ethyl
ester 28 (0.5 g, 1.0 mmol) was dissolved in pure acetic acid (20
mL), and dry sodium acetate (82 mg, 1.0 mmol) was added. The
mixture was heated under reflux for 1 h. After cooling, the
solution was added dropwise to cold aqueous ammonia (150 mL,
10%). The oily product was extracted with CH2Cl2 (3 × 20 mL),
washed with brine (30 mL), and dried over Na2SO4. After
removal of the solvent, the crude product was crystallized from
ethyl acetate to yield a white solid: yield 0.31 g, 71%; mp 231
1
°C; H NMR (CDCl3) δ 1.42 (t, J ) 6.06 Hz, 3 H), 2.10 (s, 6 H),
4.45 (q, J ) 7.06 Hz, 2 H), 5.17 (s, 4 H), 7.83 (dd, J ) 8.01, 2.20
Hz, 2 H), 8.50 (d, J ) 8.02 Hz, 2 H), 8.57 (s, 2 H), 8.90 (s, 2 H).
Ack n ow led gm en t. The research was supported by
the Fonds der Chemischen Industrie, and the Deutsche
Forschungsgemeinschaft (SFB 563, and Heisenberg
fellowship). We thank O. Nuyken for his support.
Su p p or tin g In for m a tion Ava ila ble: Characterization of
all compounds by mp, 1H and 13C NMR, GC-MS, and EA. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(35) Heller, M.; Schubert, U. S. Macromol. Symp. 2002, 177, 87.
(36) Ebmeyer, F.; Vo¨gtle, F. Chem. Ber. 1989, 122, 1725
(37) Fallahpour, R.-A. Synthesis 2000, 8, 1138.
J O0260600
8272 J . Org. Chem., Vol. 67, No. 23, 2002